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In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin.

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Presentation on theme: "In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin."— Presentation transcript:

1 In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling by Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Shigeru Kakuta, Yoichiro Iwakura, Naoya Takayama, Jun Ooehara, Makoto Otsu, Akihide Kamiya, Brian G. Petrich, Tetsumei Urano, Takafumi Kadono, Shinichi Sato, Atsu Aiba, Hiroshi Yamashita, Seiryo Sugiura, Takashi Kadowaki, Hiromitsu Nakauchi, Koji Eto, and Ryozo Nagai Blood Volume 119(8):e45-e56 February 23, 2012 ©2012 by American Society of Hematology

2 Thrombus formed by discoid platelets visualized by in vivo imaging after laser/ROS-induced injury. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

3 Inflammatory cytokines are key components for discoid platelet attachment and thrombus development in our laser/ROS-induced injury model. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

4 Analysis of TNF-α chimeric mice and the effects of TNF-α administration revealed the importance of inflammatory cytokine signaling in ECs in our thrombosis model. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

5 FACS analysis showing ROS-induced increases in VWF on HUVECs, and in P-selectin and GPIIbIIIa on mouse platelets. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

6 Flow chamber analysis of the contribution of TNF-α signaling to platelet attachment to HUVECs. (A-B) Attachment of human platelets to cultured HUVECs. Some cells were treated with si-TNF- R1 48 hours before the experiments; CTRL denotes HUVECs treated with c... Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

7 Binding of endothelial VWF to platelet GPIb plays a pivotal role in our laser/ROS-induced thrombosis model in both capillaries and arterioles. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology

8 αIIbβ3 integrin signaling and actin cytoskeletal remodeling are required for stabilization of developing thrombi in vivo. Satoshi Nishimura et al. Blood 2012;119:e45-e56 ©2012 by American Society of Hematology


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